Calretinin mediates apoptosis in small cell lung cancer cells expressing tetraspanin CD9

钙结合蛋白介导表达四跨膜蛋白 CD9 的小细胞肺癌细胞凋亡

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作者:Ping He, Hanako Kuhara, Isao Tachibana, Yingji Jin, Yoshito Takeda, Satoshi Tetsumoto, Toshiyuki Minami, Satoshi Kohmo, Haruhiko Hirata, Ryo Takahashi, Koji Inoue, Izumi Nagatomo, Hiroshi Kida, Takashi Kijima, Tetsuji Naka, Eiichi Morii, Ichiro Kawase, Atsushi Kumanogoh

Abstract

A majority of small cell lung cancer (SCLC) cells lack a metastasis suppressor, tetraspanin CD9, and CD9 expression promotes their apoptosis. By a proteomics-based approach, we compared an SCLC cell line with its CD9 transfectant and found that a calcium-binding neuronal protein, calretinin, is upregulated in CD9-positive SCLC cells. Ectopic or anticancer drug-induced CD9 expression upregulated calretinin, whereas CD9 knockdown down-regulated calretinin in SCLC cells. When calretinin was knocked down, CD9-positive SCLC cells revealed increased Akt phosphorylation and decreased apoptosis. These results suggest that CD9 positively regulates the expression of calretinin that mediates proapoptotic effect in SCLC cells.

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